부산대학교 도서관

BACKGROUND: Despite the availability of a number of antianginal agents, many patients with stable coronary artery disease (CAD) have persistent angina. Even following CABG surgery or percutaneous coronary intervention, between 25% and 60% of patients continue to suffer from angina and to require medication. Ranolazine, alone and in combination with submaximal doses of other antianginal agents, has shown anti-ischemic effects in stable CAD patients without detrimental effects on heart rate or wall stress. The efficacy of ranolazine in combination with a maximum dose of a conventional antianginal drug, however, has not been investigated. OBJECTIVE: To determine whether treatment with ranolazine reduces angina episodes in patients with symptoms that persist despite the use of the maximum recommended dose of amlodipine. DESIGN AND INTERVENTION: This was a randomized, double-blind, placebo-controlled, multinational study. Eligible patients had documented CAD, chronic stable angina (for ≥3 months), and at least three episodes of angina per week over a 2-week qualification period despite treatment with the maximum recommended dose of amlodipine (10 mg/day). Patients were randomized to ranolazine or placebo (500 mg/day for 1 week then the full 1,000 mg/day dose for 6 weeks), plus 10 mg/day amlodipine. Drug efficacy and adverse events were assessed at 2 and 6 weeks after the initiation of the full dose of ranolazine. Nitroglycerin consumption per week and the Seattle Angina Questionnaire (SAQ) were also used to assess efficacy. OUTCOME MEASURES: The primary outcome was the self-reported frequency of angina episodes per week during the 6-week full-dose treatment period. RESULTS: Of 565 patients recruited, 281 received ranolazine and 284 received placebo. The baseline characteristics of the two groups were comparable. The mean number of angina episodes at baseline was 5.63±0.18 per week, and mean nitroglycerin use was 4.72±0.21 tablets/week. Patients who received ranolazine had a significantly lower mean weekly number of angina episodes than those who received placebo (2.88±0.19 versus 3.31±0.22; P=0.028), together with a significant improvement in scores on the angina frequency dimension of the SAQ relative to placebo (22.5±19.0 versus 18.5±18.8; P=0.008). Nitroglycerin use was also lower in the ranolazine group (mean 2.03±0.20 tablets/week versus 2.68±0.22 tablets/week; P=0.014). In the subgroup analysis, patients with more than 4.5 angina episodes per week at baseline showed significant reductions in number of angina episodes per week, SAQ angina frequency and nitroglycerin use during the 6-week treatment phase, whereas those with 4.5 episodes or fewer showed significant improvements only in angina frequency. Ranolazine was well tolerated and the rate of adverse events reported was similar between the two groups. Seven patients (three in the ranolazine group and four in the placebo group) withdrew from therapy because of adverse events CONCLUSION: Ranolazine is well tolerated and reduces the incidence of angina episodes and nitroglycerin use in CAD patients with persistent angina despite receiving the maximum recommended dose of amlodipine.